Anticancer research · 2022
Isoprenylated Coumarin Exhibits Anti-proliferative Effects in Pancreatic Cancer Cells Under Nutrient Starvation by Inhibiting Autophagy.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhou Ronghao, Kusaka Erika, Wang Yin, Zhang Jing, Webb Andrew, Carrico-Moniz Dora
Аннотация
BACKGROUND/AIM: Due to the lack of early detection methods and effective treatments, pancreatic cancer has one of the lowest five-year survival rates among all cancers. We have previously identified novel isoprenylated coumarin compounds that exhibit preferential cytotoxicity against pancreatic adenocarcinoma cell line PANC-1 exclusively under glucose deprivation conditions.
MATERIALS AND METHODS: Using cell cytotoxicity assays, we investigated the anti-proliferative mechanism of our most potent isoprenylated coumarin compound of the series, DCM-MJ-I-21, with respect to time, against two other pancreatic cancer cell lines, BxPC-3 and Capan-2. We used western blotting to quantify the autophagic flux influenced by our compound, autophagy inducers (starvation and Rapamycin), and autophagy inhibitors (chloroquine and wortmannin).
RESULTS: We observed a clear dependence on glucose in DCM-MJ-I-21 in BxPC-3 and Capan-2 pancreatic cancer cell lines, suggesting that our compound targets a pathway shared by these cancer cell lines when glycolysis is not an option for survival. Our lead compound increased the conversion of LC3-I to LC3-II in PANC-1, similar to the effect of chloroquine, an autophagy inhibitor. In addition, Spautin-1, another autophagy inhibitor, showed almost the same anti-proliferative activities at the same concentration under nutrient-deprived conditions as our lead compound in both 2D and 3D cell cultures.
CONCLUSION: Our lead isoprenylated coumarin compound induces selective pancreatic cancer cell death under nutrient-deprived conditions through inhibition of autophagy, potentially providing insights into new therapeutic options.
MATERIALS AND METHODS: Using cell cytotoxicity assays, we investigated the anti-proliferative mechanism of our most potent isoprenylated coumarin compound of the series, DCM-MJ-I-21, with respect to time, against two other pancreatic cancer cell lines, BxPC-3 and Capan-2. We used western blotting to quantify the autophagic flux influenced by our compound, autophagy inducers (starvation and Rapamycin), and autophagy inhibitors (chloroquine and wortmannin).
RESULTS: We observed a clear dependence on glucose in DCM-MJ-I-21 in BxPC-3 and Capan-2 pancreatic cancer cell lines, suggesting that our compound targets a pathway shared by these cancer cell lines when glycolysis is not an option for survival. Our lead compound increased the conversion of LC3-I to LC3-II in PANC-1, similar to the effect of chloroquine, an autophagy inhibitor. In addition, Spautin-1, another autophagy inhibitor, showed almost the same anti-proliferative activities at the same concentration under nutrient-deprived conditions as our lead compound in both 2D and 3D cell cultures.
CONCLUSION: Our lead isoprenylated coumarin compound induces selective pancreatic cancer cell death under nutrient-deprived conditions through inhibition of autophagy, potentially providing insights into new therapeutic options.